Project Summary: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for various hematological diseases. However, many patients who could potentially benefit from HCT have been ineligible for the procedure due to comorbidities and age. With the development of reduced-intensity regimens and improvements in supportive care after myeloablative HCT, increasing numbers of elderly patients and those with comorbidities have been offered allogeneic HCT. Dr. Sorror, and a collaborator, Dr. R. Diaconescu, have published the first reports describing the importance of comorbidities in predicting HCT outcomes. Dr. Sorror went on to develop a new and more sensitive tool to assess comorbidities specific for recipients of allogeneic HCT. The HCT-specific-comorbidity index (HCT-CI) has created unique opportunities to better understand the impact of comorbidities on HCT outcomes and it forms the basis for this proposal. The proposal is focused on further evaluating and developing the prognostic value of comorbidities for outcomes in HCT recipients with the eventual aim of creating a universally applicable comorbidity index. During the Mentored Phase, the reliability and validity of the HCT-CI will be retrospectively tested among patients transplanted at multiple centers. In addition, scores weighting the impact of age intervals on HCT outcomes will be developed to form composite scores with the HCT-CI. Results of these studies will guide Dr. Sorror to proceed into the Independent Phase, which will address two parallel major aims. First, the biological impact of comorbidities on causes of death, particularly those associated with acute graft-versus- host-disease and organ failures, and quality of life after HCT will be assessed comparing scores from the HCT-CI to those from the comorbidity-aging composite index. This will involve both retrospective reviews of medical records of previously transplanted patients and analyses of prospective clinical trials to include larger number of patients and to ensure prospective reproducibility of the impacts of comorbidities. The second aim will prospectively investigate three different methods aimed at simplifying collection of comorbidity data and develop an educational program for evaluation of comorbidities by data registrars and, thereby, facilitate the more wide-spread incorporation of comorbidity assessment at HCT centers. Relevance: The goal of the proposal is to improve pretransplant prognostic assessment of survival and quality of life in patients with malignant and non-malignant blood disorders who are treated with allogeneic HCT and eventually establish a universally applicable comorbidity index, which will facilitate comparing results of clinical trials conducted at different academic centers.